Development of increased blood pressure in hypertensive rats is accompanied by a progressively greater cardiac mass, which involves both muscle cells and non-muscle cells. The early biochemical event of impending hypertrophy is increased RNA synthesis followed by protein synthesis in the heart. The predominating factor that determine the cardiac mass is the number of ribosomes. The work that is porposed will study the regulation of pre-rRNA, rRNA and ribosomal protein synthesis in hearts from normal and chronically hypertensive rats. The two-kidney one clip Goldblatt hypertensive rats will be employed as the experimental model to simulate high renin hypertension and the DOCA-salt hypertensive rats to simulate low renin salt-dependent hypertension. Rigorous methods will be developed to measure quantitatively the rates of synthesis of pre-rRNA and ribosomal proteins in perfused hearts and heart muscle cells. Rates of transcription from rDNA to 45S rRNA will be determined by the rate of incorporation of [3H]uridine into pre-rRNA, the specific activity of the precursor UTP during the period when labeling of pre-rRNA is rising linearly and the steady-state relationship between specific activities of UTP and UMP in pre-rRNA. Rates of mature rRNA synthesis will be measured by the rate of incorporation of [3H]uridine and [methyl-3H]methionine and the specific activity of pre-rRNA. These approaches will allow the determination of efficiency and processing of pre-rRNA to 18S and 28S rRNA. Rates of ribosomal protein synthesis will be determined by the rate of incorporation of [14C]phenylalanine into ribosomal proteins and the specific activity of phenylalanyl-tRNA. The effect of increased workload on the rates of synthesis of pre-rRNA, rRNA and ribosomal proteins will be assessed in perfused hearts by supplying a substrate and hormone mixture simulating that found in vivo. The methods developed will help to clarify the control mechanism that leads to increased production of ribosomes in hearts from chronically hypertensive rats as well as in other models of cardiac hypertrophy.